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dc.contributor.authorWang, Xiaojuan
dc.contributor.authorCui, Yanyan
dc.contributor.authorLuo, Gaoxing
dc.contributor.authorWang, Qinghong
dc.contributor.authorHu, Jie
dc.contributor.authorHe, Weifeng
dc.contributor.authorYuan, Jun
dc.contributor.authorZhou, Junyi
dc.contributor.authorWu, Yan
dc.contributor.authorSun, Xiaofeng
dc.contributor.authorRobson, Simon C
dc.contributor.authorLi, Xianchang
dc.contributor.authorTan, Jiangling
dc.contributor.authorPeng, Yanmeng
dc.contributor.authorXue, Gang
dc.contributor.authorLu, Linrong
dc.contributor.authorGao, Wenda
dc.contributor.authorWu, Jun
dc.date.accessioned2013-04-24T20:52:12Z
dc.date.issued2012
dc.identifier.citationWang, Xiaojuan, Yanyan Cui, Gaoxing Luo, Qinghong Wang, Jie Hu, Weifeng He, Jun Yuan, et al. 2012. Activated mouse \(CD4^+Foxp3^−\) T cells facilitate melanoma metastasis via Qa-1-dependent suppression of NK-cell cytotoxicity. Cell Research 22(12): 1696-1706.en_US
dc.identifier.issn1001-0602en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:10582119
dc.description.abstractThe regulatory activities of mouse \(CD^4+Foxp3^+\) T cells on various immune cells, including NK cells, have been well documented. Under some conditions, conventional \(CD4^+Foxp3^−\) T cells in the periphery are able to acquire inhibitory function on other T cells, but their roles in controlling innate immune cells are poorly defined. As a potential cellular therapy for cancer, ex vivo activated \(CD4^+Foxp3^−\) effector T cells are often infused back in vivo to suppress tumor growth and metastasis. Whether such activated T cells could affect NK-cell control of tumorigenesis is unclear. In the present study, we found that mitogen-activated \(CD4^+Foxp3^−\) T cells exhibited potent suppressor function on NK-cell proliferation and cytotoxicity in vitro, and notably facilitated B16 melanoma metastasis in vivo. Suppression of NK cells by activated \(CD4^+Foxp3^−\) T cells is cell-cell contact dependent and is mediated by Qa-1:NKG2A interaction, as administration of antibodies blocking either Qa-1 or NKG2A could completely reverse this suppression, and significantly inhibited otherwise facilitated melanoma metastasis. Moreover, activated \(CD4^+Foxp3^−\) cells from Qa-1 knockout mice completely lost the suppressor activity on NK cells, and failed to facilitate melanoma metastasis when transferred in vivo. Taken together, our findings indicate that innate anti-tumor response is counter regulated by the activation of adaptive immunity, a phenomenon we term as “activation-induced inhibition”. Thus, the regulatory role of activated \(CD4^+Foxp3^−\) T cells in NK-cell activity must be taken into consideration in the future design of cancer therapies.en_US
dc.language.isoen_USen_US
dc.publisherNature Publishing Groupen_US
dc.relation.isversionofdoi:10.1038/cr.2012.128en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3515753/pdf/en_US
dash.licenseLAA
dc.subjectNK cellsen_US
dc.subjectT cellsen_US
dc.subjectsuppressionen_US
dc.subjectmelanomaen_US
dc.subjectmetastasisen_US
dc.subjectQa-1en_US
dc.titleActivated mouse \(CD4^+Foxp3^−\) T cells facilitate melanoma metastasis via Qa-1-dependent suppression of NK-cell cytotoxicityen_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalCell Researchen_US
dash.depositing.authorWu, Yan
dc.date.available2013-04-24T20:52:12Z
dc.identifier.doi10.1038/cr.2012.128*
dash.authorsorderedfalse
dash.contributor.affiliatedSun, X
dash.contributor.affiliatedWu, Yan
dash.contributor.affiliatedRobson, Simon


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